The invention relates to compositions and methods of use of ester prodrug derivatives of L-dopa for enhancing absorption via rectal therapeutic application. More specifically, the invention relates to alkyl, aryl, substituted and unsubstituted mono-, di- and polyhydroxyalkyl, and substituted and unsubstituted aralkyl esters of L-dopa and their Pharmaceutically acceptable counterion salts. Also, the heretofore disclosed compositions and methods may optionally include a decarboxylase inhibitor such as carbidopa and benserazide. The inhibitor serves three vital roles, namely, (1.) prevents the breakdown of L-dopa, (2.) reduces commonly know side effects, and (3.) allows further expression of L-dopa pharmacological activity.
L-dopa is usually orally given with a L-amino acid decarboxylase inhibitor. Given in this fashion, L-dopa is effective in the treatment of Parkinson's disease. However, presumably due to erratic absorption and blood levels, control of disease symptoms is not always adequate. L-dopa esters have not provided significant advantages when given orally. This is probably due to ester hydrolysis in the g.i. tract and/or presystemic metabolism. These problems are ameliorated by the rectal route.
As employed in this application, the expression "prodrug" denotes a derivative of a known and proven prior art compound, which derivative, when absorbed into the bloodstream of a warm-blooded animal, "cleaves" in such a manner as to release the proven drug form and permits the same to afford improved therapeutic efficacy than that which could be obtained if the proven drug form, per se, was administered.
Also as employed in this application, the term "cleavage" denotes that the proven drug form is released and the remaining "cleaved" moiety is nontoxic and metabolized in such a manner that non-toxic, metabolic Products are produced.